Complement comprises a group of over 30 soluble and cell surface proteins that represent a major effector arm of the immune system. Although complement is an important component of the immune system, complement-mediated inflammation plays a role in several inflammatory and auto-immune disorders. There is great interest in developing inhibitors of complement for the treatment of autoimmune and inflammatory disease, and also for use in preventing organ rejection in xenotransplantation.
Vaccinia virus complement control protein (VCP) is known to be a strong inhibitor of the classical, lectin and alternative pathways of complement, acting on both C4 and C3. As such, VCP is a promising candidate for use as a complement inhibitor. Although VCP is an inhibitor of complement activation, it would be beneficial to further improve complement inhibition activity of VCP.
VCP is the naturally occurring protein. rVCP is a protein expressed in a yeast/heterologous system and has the same sequence as natural VCP. The humanised recombinant vaccinia virus complement control protein (hrVCP) of the invention has three amino acid changes as described below.